The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority.
Our results identify Cul4b(Δ)/Y mice as a potential model for the non-syndromic model of XLMR that replicates the CUL4B-associated MR and is valuable for the development of a therapeutic strategy for treating MR.
We discuss the unexpected association of defective CUL4B with syndromal X-linked mental retardation in humans and speculate on the biochemical consequences and clinical implications of defective CRL4 function.